Differential Expression of CXCL12 and CXCR4 During Human Fetal Neural Progenitor Cell Differentiation

Abstract

Stromal cell-derived factor 1 alpha (SDF-1α, CXCL12) and its receptor CXCR4 play an important role in the central nervous system (CNS) development and adulthood by mediating cell migration, enhancing precursor cell proliferation, assisting in neuronal circuit formation, and possibly regulating migration during repair. The expression pattern of CXCR4 and CXCL12 during neurogenesis has not been thoroughly elucidated. In this study, we investigated the expression of CXCL12 and CXCR4 during neural progenitor cells (NPC) differentiation by microarray analysis and reverse transcriptasepolymerase chain reaction (RT-PCR) using human fetal NPC as a model system. The production of CXCL12 was measured by enzyme-linked immunosorbent assay (ELISA). CXCR4 expression was determined by florescence-activated cell sorting (FACS) analysis, immunocytochemical staining, and CXCR4-mediated inhibition of cyclic AMP (cAMP) accumulation. Our data demonstrated that CXCR4 expression is significantly upregulated when NPC are differentiated into neuronal precursors, whereas CXCL12 is upregulated when differentiated into astrocytes. We also provide evidence that CXCR4 localization changes as neurons mature. In neuronal precursors, CXCR4 is localized in both neuronal processes and the cell body, whereas in mature neurons, it is primarily expressed on axons and dendrites. This differential expression of CXCR4 and CXCL12 may be important for the temporal regulation of neuronal migration and circuit formation during development and possibly in adult neurogenesis and repair.

Strain Differences in Behavioral and Cellular Responses to Perinatal Hypoxia and Relationships to Neural Stem Cell Survival and Self-Renewal

“…This finding is consistent with our hypothesis that the behavioral data exhibited by the C57 pups may be a consequence of their relative lower proliferative and migratory rates and higher susceptibility to undergo apoptosis in response to a reduction in O 2 % because of their relatively blunted HIF-1␣ response compared with that of CD-1 pups and in part mediated by their blunted response to SDF-1. 59 Interestingly, we observed increased glial and neuronal differentiation (a process known to be affected by SDF-1-CXCR4 signaling) 60 in C57 NSCs after radial migration outward from cultured neurospheres, suggesting that in addition to the other above-mentioned factors that may influence their responsiveness to a hypoxic insult, the earlier progression of the c57 NSCs to neuronal differentiation (evidenced by increased GFAP and ␤-tubulin III expression) may influence their migration and hence their ability to affect optimal recovery after a hypoxic insult in vivo.…”

Constraint-Induced Movement Therapy Enhanced Neurogenesis and Behavioral Recovery after Stroke in Adult Rats

“…Stromal cell-derived factor 1 (SDF-1) and its receptor CXCR4 were found to play an important role in both the developing brain and adult brain (Lu et al 2002;Peng et al 2007;Stumm and Hollt 2007;Bhattacharyya et al 2008). SDF-1 and CXCR4 were highly expressed throughout the SVZ and subgranular zone of the dentate gyrus and involved in the migration, proliferation, differentiation of neural progenitor/stem cell (Lu et al 2002;Stumm et al 2002;Tissir et al 2004;Bhattacharyya et al 2008).…”

Association analysis between pseudorabies antibody and five single-nucleotide polymorphisms in pigs

“…The chemokine stromal cellderived factor 1 (SDF-1, CXCL12), a member of the CXC chemokine family, plays an important role in both the developing brain and adult CNS. Both in vivo and in vitro studies suggest that CXCL12 and its ligand CXCR4 are involved in neurogenesis processes such as neural progenitor/stem cell migration, proliferation and differentiation (Lu et al, 2002;Peng et al, 2007). In addition, it is a key regulator of B-cell lymphopoiesis, hematopoietic stem cell mobilization and leukocyte migration.…”